Stromal Cell-Derived Factor 1 Promotes Cell Migration to Enhance Bone Regeneration After Hypoxic Preconditioning

Abstract

One of the major problems in bone regeneration is that seeded cells do not effectively infiltrate into the central scaffolds. In this study, we generated chitosan/gelatin scaffolds (C group), and investigated whether exogenous addition of stromal cell-derived factor 1 (SDF-1) in the scaffolds (S group) and additional hypoxic preconditioning (S/P group) could enhance bone regeneration by promoting cell migration of rat bone marrow stromal cells (BMSCs). SDF-1 effectively promoted cell migration in vitro and this effect was further enhanced by hypoxic preconditioning. The S/P group had a better cell viability than the other two groups (all p < 0.05). Moreover, hypoxia-inducible factor 1 α and CXC chemokine receptor 4 (CXCR4) in BMSCs were significantly higher in the S/P group. For in vivo studies, bone regeneration ability was evaluated at 7, 14, and 21 days by microcomputed tomography. The S/P group showed a statistically greater amount of bone formation compared to the C group and S group at each time point (all p < 0.05). While the C group was still poorly healed for calvarial defect after 3 weeks, the S/P group demonstrated the most effective bone healing with only a smaller translucent area in the fracture area. Our results confirm that SDF-1/CXCR4 signaling promotes cell migration to the central scaffold after hypoxic preconditioning and enhances bone regeneration.

Impact Statement

Current tissue engineering strategies have progressed recently from a historical approach that is based primarily on biomaterials to a cell- and tissue-based approach. Essentially all orthopedic tissue engineering strategies can be distilled to a strategy or combination of strategies that seek to increase the number or relative performance of bone-forming cells. In our study, we explored a “cell guidance” approach using a chemokine, SDF-1α, to promote cell migration to the central scaffold, to enhance bone regeneration. In our opinion, SDF-1α is a promising candidate for in situ recruitment of bone-forming cells in regenerative therapies under hypoxia precondition.